P542: REAL WORLD OUTCOMES FOR PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA IN BRITISH COLUMBIA (BC): EXCELLENT OUTCOMES WITH LOW EARLY DEATH RATE AND HIGH OVERALL SURVIVAL IN A POPULATION BASED STUDY
Authors: R. Henderson, Y. Eissa, R. Stubbins, Y. Abou Mourad, S. Chung, D. Forrest, K. Hay, F. Kuchenbauer, S. Nantel, T. Nevill, M. Power, J. Rodrigo, C. Roy, D. Sanford, K. Song, H. Sutherland, C. Toze, J. White, S. Narayanan
Journal: HemaSphere (2022)

Background: Acute promyelocytic leukaemia (APL) therapy has significantly improved with the use of All trans retinoic acid (ATRA) and Arsenic Trioxide (ATO) for low risk disease (Lo-Coco 2013). Treatment of high risk disease remains more challenging with a higher risk of early mortality & greater concern of relapse. All patients (pts) with APL in British Columbia, Canada are treated by the Leukemia/BMT Program at Vancouver General Hospital, Vancouver. Since 2014, all pts have received ATRA/ATO based therapy based on the Le-Coco study. Pts with high risk disease (WCC > 10 x 109/L at presentation) also receive a 3 day course of doxorubicin (60mg/m2) for induction only. Aims: We sought to review treatment outcomes since initiating these treatment protocols with emphasis on drug toxicities, dose modifications & management of high risk & elderly patients in order to describe real world outcomes. Methods: Ethics was approved by the board of the BCCA and UBC. Data was collected by chart reviews, hospital databases & collated on a central file. Demographics, risk stratification, treatment received, adverse events & survival was collected & analysis performed on Microsoft excel v16.57 & SPSS Statistics v28.0.1.1. Kaplan Meier curves were performed for PFS & OS, student t and chi squared tests were performed to assess differences between subgroups. Results: We identified 67 pts with APL during the study period. 40% were male 60% female, the median age was 61 yrs. (21-83yo). 36(54%) pts were > 60 yrs at diagnosis. The median duration of follow up was 2.9 yrs. All had molecular confirmation of disease. 16(24%) pts had high risk disease at diagnosis. At time of censor overall survival was 97% and PFS 94%. 55(82%) pts had a documented toxicity. Common toxicities included differentiation syndrome (DS) in 27(40%) pts, hepatotoxicity 17 (25%), QTc prolongation 13(19%) & neurological effects 9 (13%). Infections were documented in 40(59%) pts including bacterial infections in 25 patients (37%), culture negative febrile neutropenia in 12 (20%), viral infections in 5 (7%) & fungal infections in 1 (1.5%). Clinically significant bleeding was documented in 10 (15%) of patients, 5 of which were CNS/retinal bleeds. DS was more common in high risk disease though this difference was not statistically significant (p=0.365). 8(30%) pts with DS needed ICU admission. There were 2 early deaths, in the cohort, both in pts > 75 yo with high risk disease due to multi-organ failure and bleeding within 5 days of presentation. Dose modifications were assessed in 64 pts (2 deaths & one lost to follow up). 37 (58%) were described as having had a dose modification. 13 (20%) had a reduction in treatment dose, 16(25%) had doses/days of drug omitted. 6(9%) had reductions in dose and omissions. The most common reasons for dose modifications were DS 12(19%), QTc prolongation 10 (15%) & hepatotoxicity 8 (12%). Pts over 60yo were more likely to have a dose modification than pts below 60yo (73% vs 43% p = 0.014). 65 pts diagnosed achieved morphological remission & 64 a molecular remission at the end of planned therapy. 2 relapses occurred in our cohort, 1 had a concomitant cytogenetic abnormality incorporating a Tp53 deletion. The second initially received ATRA only induction due to age & comorbidity. Summary/Conclusion: This real world, population based data for patients with APL in BC confirms high response rates, survival and relatively low early death rate and acceptable toxicity even in older patients with high risk disease and comorbidities. In our cohort appropriate dose modifications did not impact remission or relapse rates.